Journal of Inflammation Research
·
2022
·
IF 4.631
Meng Zhang,Yi Liu,Jing Chen,Lei Chen,Li Zhang,Xianguo Chen,Zongyao Hao,Chaozhao Liang
Background Chronic nonbacterial prostatitis (CNP) has a high incidence, low cure rate, and unclear pathogenesis. Here, we aimed to systematically identify effective diagnostic and therapeutic targets for CNP.Methods Prostate tissues were obtained from established mouse models and negative controls and were used for mRNA array sequencing and immunohistochemistry (IHC) staining. Predominant pathways were identified based on pathway enrichment analysis and pharmaceutical experiments. We also investigated the functional role of CXCL12 on CP, a critical factor belonging to the predominant chemotaxis pathway, and employed IHC staining to explore the influence of the CXCL12/CXCR4 axis on the activation of the NF-κB, AKT, and STAT3 signaling pathways. Serum samples derived from both CNP cases and healthy controls were used to determine the secretion level of CXCL12.Results By employing mRNA array sequencing and immunohistochemistry, we found that CXCR4, CXCL12, CD44, and OFLM4 were highly expressed in the infiltrated inflammatory T cells of the prostate tissues generated from CNP mice, while they were rarely expressed on the epithelial cells. Based on the pathway enrichment results, we applied pathway inhibitors to suppress the activity of these classic pathways. We found that targeting the CXCL12/CXCR4 axis with its specific antagonist AMD3100 remarkably alleviated inflammatory infiltration of the prostate in CNP models. Similar results were obtained when we replaced AMD3100 with adenovirus-associated virus (AAV)-shCxcl12. To clarify the potential mechanisms of how the CXCL12/CXCR4 axis influences the pathogenesis of CNP, we tested the classical downstream pathways. The results suggested that p-Akt, p-STAT3, and p-NF-κB were more highly expressed on the inflammatory cells of the prostate derived from the CNP model and were partly suppressed after applying AMD3100 or delivering AAV-shCxcl12, indicating that the CXCL12/CXCR4 axis potentially functioned through AKT/NF-κB and STAT3 signaling to influence the pathogenesis of CNP.Conclusion Our study provides potential diagnostic biomarkers and therapeutic targets for CNP.
研究领域:
免疫学
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分子生物学
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药理学
·
泌尿学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Zi Ye,Leilei Yu,Chuan Zhang,Xiaojing Wei,Jianxin Zhao,Wei Chen,Qixiao Zhai,Fengwei Tian
Volvaria volvacea polysaccharides (VVP) possess diverse bioactivities with promising applications in biomedicine and functional foods. This study investigated the metabolic fate of VVP in human gut microbiota and uncovered the pivotal role of Bacteroides thetaiotaomicron using in vitro fecal fermentation models. VVP selectively promoted B. thetaiotaomicron proliferation, establishing it as a central hub in microbial interaction networks. Metabolomic profiling revealed significant increases in short-chain fatty acids (SCFAs) and adenosine during VVP fermentation. KEGG pathway enrichment demonstrated activation of starch and sucrose metabolism and histidine biosynthesis, consistent with PICRUSt functional predictions. Network correlation and sole‑carbon source assays confirmed B. thetaiotaomicron as a key VVP degrader. These findings establish B. thetaiotaomicron as a dual-function mediator that orchestrates VVP bioconversion into bioactive metabolites and reshapes gut microenvironment. This mechanistic framework supports the development of VVP-based, microbiota-targeted interventions to enhance gut health.
研究领域:
微生物学
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糖生物学
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代谢组学
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功能性食品
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生物医学
✓ 已验证
DOI
PubMed
高影响因子
AIP Advances
·
2025
·Vol. 15
·期 7
·
IF 1.4
Yu Dong-hua,Wang Yu,Yu Chun-Miao,Zhou Qi,Liu Shu-min,Liu Ting-ting
The aim of this study is to construct a competitive endogenous RNA regulatory network of gouty arthritis through transcriptomics and investigate its underlying pathogenesis. Transcriptomics was performed with the rats’ joints in both the control and model groups. The mRNA, miRNA, lncRNA, and circRNA were analyzed using the R language. The RNA data were visualized as the ceRNA network. Genes were combined, the KEGG pathway was enriched, and the first five pathways were selected. Meanwhile, relationships between genes in the extraction pathway were integrated into a network, and key genes were mapped. mRNA, lncRNA, and circRNA were scored to compare the conservatism of RNA. Finally, lncRNA, circRNA, miRNA, and genes were considered the core, and information about other differential RNAs having a targeted relationship with them (i.e., host genes) was added. Based on ceRNA analysis, the relationship pairs between lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA were extracted. A total of 1165 de-mRNAs, 91 de-miRNAs, 456 de-lncRNAs, and 70 de-circRNAs were selected. The key genes were identified for pathway enrichment, such as the phospholipase D signaling pathway and endocytosis. Based on the ceRNA analysis, the networks of lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA were constructed. The differentially expressed RNAs between the control and model groups were identified using the transcriptomics of ankle tissue. The findings indicate that mRNA, lncRNA, and circRNA can competitively bind to GA-related miRNAs, leading to mutual regulatory effects. The RNAs identified from the constructed lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA networks are potential targets for therapeutic drugs and may be involved in the pathogenesis of GA.
研究领域:
分子生物学
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基因组学
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生物信息学
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RNA生物学
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免疫学
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关节炎研究
✓ 已验证
产品关联
DOI
高影响因子
Heliyon
·
2024
·
IF 3.4
Zhihao Zhang,Feng Liu,Xin Lan,Fuhai Wang,Jiahao Sun,Honglong Wei
Objective This study explores the impact of pyroptosis-related genes (PRG) on the prognosis of liver cancer (LC). Methods 421 samples (371 tumor samples and 50 normal samples) from the Cancer Genome Atlas (TCGA) were included in this study. GSE14520 dataset (data of RNA expression and relevant clinicopathological features), GSE125449 dataset (single-cell data in LC) and HCCDB18 dataset (validation on the reliability of the model) were downloaded as appropriate. Download the PRG and its corresponding pathway information from the gene set enrichment analysis (GSEA) website. The consensus clustering was performed by ConsensusClusterPlus package. Differentially expressed genes (DEGs) were identified using limma package, and prognostic features were constructed using un/multivariate and Lasso Cox regression. Pathway enrichment analysis was conducted by ssGSEA method. Receiver Operating Characteristic and the survival analysis were conducted by timeROC and Survminer packages. The Seurat package was used for single-cell RNA sequencing (scRNA-seq) analysis. For cellular validation, following the quantification on the key genes via reverse-transcription quantitative PCR, the Transwell and scratch assays were applied to evaluate the in-vitro invasion and migration of LC cells Huh-7. Results 12 prognosis-related genes were identified to be related to the progression of LC. Three subtypes including C1, C2 and C3 were categorized using the 12 prognosis-related genes and PRGs significantly related to the prognosis of LC patients. The worst and best prognosis was seen in C3 subtype and C2 subtype, respectively. Hallmark pathway enrichment analysis has shown the concurrent immunoactivation and immune escape in C3 subtype. A RiskScore model was constructed using 8 key genes (KPNA2, UCK2, FTCD, CBX2, RAB32, HMMR, S100A9 and ANXA10) from the DEGs of three subtypes. The RiskScore system as an independent prognostic factor dividing the patients into high and low risk groups, and patients of the high-risk group had poor prognosis in both test set and validation set. A nomogram model combining the risk score had the extreme higher benefit. Further, 6 subclusters were identified from scRNA-seq analysis, where the highest PYROPTOSIS score was seen in Monocytic-Macrophages. The quantification on the key genes has suggested the high expressions of KPNA2, UCK2, CBX2, RAB32, HMMR and S100A9 and the low expressions of FTCD and ANXA10 in LC cells Huh-7. Particularly, UCK2 knockdown evidently diminished the number of invaded and migrated LC cells in vitro . Conclusion The risk model associated with pyproptosis is crucial for the tumor immunity of LC and may serve as a prognostic indicator for patients suffering from LC. Our findings will offer new perspectives for immunotherapies targeting LC.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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癌症基因组学
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细胞免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Zhang Xiuying,Chen Qilei,Zhao Jia,Zhao Wei,Fan Ni,Wang Yu,Chen Hubiao,Rong Jianhui
Myocardial infarction (MI) is a highly prevalent and lethal disease worldwide. Prevention and timely recovery are critical for the control of the recurrence and heart failure in MI survivors. The present study was designed to investigate the cardioprotective activity of the herbal medicine formula Baoyuan Decoction (BYD) and identify the active compounds and molecular targets. The ethanolic BYD extract (BYDE) was prepared by water extraction and ethanol precipitation of four herbal medicines, Astragali Radix, Ginseng Radix et Rhizoma, Cinnamomi Cortex, and Glycyrrhizae Radix et Rhizoma. Initially, BYDE was validated for the cardioprotective effectiveness in a mouse model of ischemia injury and rat cardiomyocyte H9C2 cells. As results, BYDE effectively reduced infarct size from 56% to 37% and preserved cardiac functions in mouse MI model while protected H9C2 cells against oxygen glucose deprivation. Subsequent network pharmacology analysis revealed that 122 bioactive ingredients, including flavonoids and saponins from the UPLC-MS/MS profile of BYDE, might target 37 MI-related proteins, including inflammatory and apoptotic mediators (e.g., TNF, NFKB1, CASPs, TNFRSF1A, CXCL12, BCL2A1). Pathway enrichment analysis suggested that BYDE might control the cardiac inflammation via targeting the tumor necrosis factor-alpha (TNF-α)/nuclear factor-κB (NF-κB) pathway while the selected targets were also implicated in IL-17 signaling pathway, lipid and atherosclerosis. Consequently, adenosine, ginsenoside Rh2, isoliquiritigenin, and licochalcone A were selected to generate the four-compound mixture AGILe and validated for the inhibitory effects on the TNF-α/NF-κB pathway. The results of the present study suggested that the mixture AGILe might be a potential cardioprotective remedy against MI.
研究领域:
药理学
·
心脏病学
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中医药
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分子生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2019
·
IF 1.984
Yueying Tao,Kunming Tian,Ji Chen,Danfeng Tan,Yan Liu,Yongai Xiong,Zehui Chen,Yingbiao Tian
This study aims to predict the active ingredients, potential targets, signaling pathways and investigate the “ingredient-target-pathway” mechanisms involved in the pharmacological action of Danshiliuhao Granule (DSLHG) on liver fibrosis. Pharmacodynamics studies on rats with liver fibrosis showed that DSLHG generated an obvious anti-liver fibrosis action. On this basis, we explored the possible mechanisms underlying its antifibrosis effect using network pharmacology approach. Information about compounds of herbs in DSLHG was collected from TCMSP public database and literature. Furthermore, the oral bioavailability (OB) and drug-likeness (DL) were screened according to ADME features. Compounds with OB≥30% and DL≥0.18 were selected as active ingredients. Then, the potential targets of the active compounds were predicted by pharmacophore mapping approach and mapped with the target genes of the specific disease. The compound-target network and Protein-Protein Interaction (PPI) network were built by Cytoscape software. The core targets were selected by degree values. Furthermore, GO biological process analysis and KEGG pathway enrichment analysis were carried out to investigate the possible mechanisms involved in the anti-hepatic fibrosis effect of DSLHG. The predicted results showed that there were 108 main active components in the DSLHG formula. Moreover, there were 192 potential targets regulated by DSLHG, of which 86 were related to liver fibrosis, including AKT1, EGFR, and IGF1R. Mechanistically, the anti-liver fibrosis effect of DSLHG was exerted by interfering with 47 signaling pathways, such as PI3K-Akt, FoxO signaling pathway, and Ras signaling pathway. Network analysis showed that DSLHG could generate the antifibrosis action by affecting multiple targets and multiple pathways, which reflects the multicomponent, multitarget, and multichannel characteristics of traditional Chinese medicine and provides novel basis to clarify the mechanisms of anti-liver fibrosis of DSLHG.
研究领域:
药理学
·
中药学
·
分子生物学
·
系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Du Hongxu,Li Zhangxun,Su Lijuan,He Zhengke,Tan Xiaoyan,Hou Fengzhi,He Tanjie,Pan Yu,Xu Shuang,Cao Liting,Dong Shiqi,Ma Yue
Objective: To investigate the anti-inflammatory activity and mechanism of Baicalin derivative (Baicalin butyl ester, BE).Methods: BE was synthesized and identified using UV-Vis spectroscopy, FT-IR spectroscopy, mass spectrometry (MS) and high-performance liquid chromatography (HPLC) methods. Its anti-inflammatory potential was explored by an in vitro inflammation model. Network pharmacology was employed to predict the anti-inflammatory targets of BE, construct protein-protein interaction (PPI) networks, and analysis topological features and KEGG pathway enrichment. Additionally, molecular docking was conducted to evaluate the binding affinity between BE and its core targets. qRT-PCR analysis was conducted to validate the network pharmacology results. The organizational efficiency was further evaluated through octanol-water partition coefficient and transmembrane activity analysis.Results: UV-Vis, FT-IR, MS, and HPLC analyses confirmed the successfully synthesis of BE with a high purity of 93.75%. In vitro anti-inflammatory research showed that BE could more effectively suppress the expression of NO, COX-2, IL-6, IL-1β, and iNOS. Network pharmacology and in vitro experiments validated that BE’s anti-inflammatory effects was mediated through the suppression of SRC, HSP90AA1, PIK3CA, JAK2, AKT1, and NF-κB via PI3K-AKT pathway. Molecular docking results revealed that the binding affinities of BA to the core targets were lower than those of BE. The Log p-value of BE (1.7) was markedly higher than that of BA (−0.5). Furthermore, BE accumulated in cells at a level approximately 200 times greater than BA.Conclusion: BE exhibits stronger anti-inflammatory activity relative to BA, possibly attributed to its better lipid solubility and cellular penetration capabilities. The anti-inflammatory mechanism of BE may be mediated through the PI3K-AKT pathway.
研究领域:
药理学
·
化学
·
分子生物学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2021
·
IF 5.34
Jin-hua Fan,Min-min Xu,Li-ming Zhou,Zheng-wei Gui,Lu Huang,Xue-gang Li,Xiao-li Ye
Background and purpose Zuojin capsule (ZJC), a classical prescription, is outstanding in improving the conditions of patients with gastrointestinal diseases and colorectal cancer (CRC). Although ZJC has multi-ingredient and multi-target characteristics, its pharmacological effect on colorectal cancer and the underlying mechanism remain unclear. Method Here, the activity of ZJC against CRC was evaluated by the experiments with CRC cells and HCT-116 xenografted mice. The key genes of CRC were obtained from the cancer genome atlas (TCGA). The genes potentially targeted by ZJC were collected from traditional Chinese medicine systems pharmacology (TCMSP) database. The underlying pathways related to selected targets were analyzed through gene ontology (GO) and pathway enrichment analyses. Western blot (WB), cellular thermal shift assay (CETSA), molecular docking and quantitative real-time PCR (QRT-PCR) were carried out to confirm the validity of the targets. Results In vitro and in vivo results indicated that ZJC may inhibit CRC cells and tumor growth. The network pharmacological analysis indicated that 22 compounds, 51 targets and 20 pathways were involved in the compound-target-pathway network. Our results confirmed that ZJC inhibited cycle progression, migration and induced apoptosis by targeting candidate genes ( CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 , and MMP9 ). We found that ZJC could directly change the protein level by regulating the protein stability and transcriptional activity of the target. Conclusions In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. The results of this study provide a basic theory for the clinical trials of Zuojin Capsules against colorectal cancer.
研究领域:
药理学
·
肿瘤学
·
系统生物学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）